Risk for colon cancer appears to be associated with increased and abnormal colonic epithelial cell proliferation. Extensive laboratory experimentation has demonstrated that the process of carcinogenesis in many organs, including the colon, is dependent on intact activity of the enzyme ornithine decarboxylase (ODC) and subsequent synthesis of polyamines. Inhibition of this biochemical pathway with DFMO blocks the development of tumors in nearly all animal models tested, including specific chemically- induced tumors of the colon. We there fore plan to test the efficacy of DFMO in modulating measures of polyamine synthesis (ODC activity, polyamine content) and epithelial cell proliferation (crypt [3H] thymidine labeling) for rectal mucosal biopsies. Patients between the ages of 40 and 80 who have had a colon polyp removed in the prior 3 months will be the subject population. Two major trials will be sequentially conducted. In the first study the initial group of 10 subjects will received a dose of DFMO which would be regarded as the highest desirable in a chemoprevention trial. The drug will be given for one months and the level of polyamine synthesis and cellular proliferation measured in rectal mucosal biopsies pre and post treatment. The dose of DFMO will be decreased in each subsequent group of 10 patients until no effect on polyamine synthesis and cellular proliferation is demonstrated. A dose at which 25% inhibition of these biochemical markers is consistently seen will be used for a longer term phase IIb trial. In this study, 100 patients will be randomly assigned to placebo and DFMO groups and the effects on biochemical markers measured over a two year period. The effects on the indicated biochemical parameters in the rectal mucosal biopsies will be correlated to levels of polyamine synthesis in other more easily accessible tissues, including epithelial cells from the buccal mucosal and buffy coat leukocytes. Serum DFMO levels will be used as a marker of dosing compliance as well. The demonstration of consistent inhibition of polyamine synthesis and cellular proliferation in the treatment group will serve as the basis for planning a subsequent randomized, placebo-controlled will serve as the basis for planning a subsequent randomized, placebo-controlled phase III prevention trial in which colon polyp recurrence will serve as a surrogate indicator of colon cancer risk.